This proposal seeks to define abnormalities of production, transport or action of estrogens and androgens associated with cancer of the endometrium, breast and prostate, as well as the sex associated autoimmune diseases, particularly lupus. A primate model suitable for study of peripheral estrogen synthesis and estrogen transport will be established. A new etiologic hypothesis implicating an increase in the percent free estradiol due to metabolic and other disorders, such as obesity and hypothyroidism, will be tested using serum free patients and those at high risk for cancer development. Studies of the interaction of sex steroids with the immune system will be carried out in the murine lupus model (NZB/NZW f1) as well as with peripheral lymphocytes from patients. Based on our hormone receptor studies, the possibility that antiestrogen--progestin treatment may reverse cervico-vaginal abnormalities induced by neonatal DES treatment of mice will be explored. Finally human SHBG will be purified to homogeneity in order to prepare antibodies so that a method for measurement independent of ligand binding may be developed.